Bone/polyurethane composites and methods thereof

Abstract

Present inventions present composites of bone particles and polyurethane(s), as well as methods of making such composite and uses thereof. A porous composite comprises a plurality of bone particles; and polyurethanes with which the bone particles are combined. To prepare a porous composite, a composition comprise a plurality of bone particles, polyurethane precursors including polyisocyanate prepolymers and polyols, water and catalyst. A composition is either naturally moldable and/or injectable, or it can be made moldable and/or injectable. After implantation or injection, a composition may be set to form a porous composite that provides mechanical strength and supports the in-growth of cells. Inventive composites have the advantage of being able to fill irregularly shape implantation site while at the same time being settable to provide the mechanical strength for most orthopedic applications.

What is claimed is: 
     
       1. A biodegradable composite, comprising:
 a plurality of bone particles; 
 a NCO-terminated prepolymer, the NCO-terminated prepolymer comprising a polyisocyanate that includes about 10 wt % to about 55 wt % NCO and a first polyol that includes a molecular weight of about 100 g/mol to about 1000 g/mol; and 
 a second polyol; 
 wherein the composite in a hardened state is biodegradable and has a porosity of at least 3%. 
 
     
     
       2. The composite of  claim 1 , wherein the bone particles comprise cortical bone, cancellous bone, cortico-cancellous bone, or combinations thereof. 
     
     
       3. The composite of  claim 1 , wherein the bone particles comprise autogenous bone, allogenic bone, xenogenic bone, or combinations thereof. 
     
     
       4. The composite of  claim 1 , wherein the bone particles are nondemineralized, superficially, partially or fully demineralized. 
     
     
       5. The composite of  claim 1 , wherein the bone particles are surface demineralized. 
     
     
       6. The composite of  claim 1 , comprising at least approximately 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %, 70 wt %, 80 wt %, or 90 wt % of bone particles. 
     
     
       7. The composite of  claim 1 , comprising at least approximately 30 vol %, 35 vol %, 40 vol %, 50 vol %, or 60 vol % of bone particles. 
     
     
       8. The composite of  claim 1 , further comprising an inorganic material. 
     
     
       9. The composite of  claim 8 , wherein the inorganic material is selected from the group consisting of aragonite, dahlite, calcite, amorphous calcium carbonate, vaterite, weddellite, whewellite, struvite, urate, ferrihydrite, francolite, mono hydro calcite, magnetite, goethite, dentin, calcium carbonate, calcium sulfate, calcium phosphosilicate, sodium phosphate, calcium aluminate, calcium phosphate, hydroxyapatite, α-tricalcium phosphate, dicalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, amorphous calcium phosphate, octacalcium phosphate (OCP), calcium phosphate silica glass, fluoroapatite, chloroapatite, magnesium substituted tricalcium phosphate, carbonate hydroxyapatite, and combinations and derivatives thereof. 
     
     
       10. The composite of  claim 1 , further comprising one or more of serum albumin, collagen, an extracellular matrix component, a synthetic polymer, and a naturally-derived polymer. 
     
     
       11. The composite of  claim 1 , wherein the second polyol comprises a polymer selected from the group consisting of poly(caprolactones), poly(lactide), poly(glycolide), polyglyconate, poly(arylates), poly(anhydrides), poly(hydroxy acids), polyesters, poly(ortho esters), poly(alkylene oxides), polycarbonates, poly(propylene fumarates), poly(propylene glycol-co fumaric acid), polyamides, polyethers, polyureas, polyamines, polyamino acids, polyacetals, poly(orthoesters), poly(pyrolic acid), poly(glaxanone), poly(phosphazenes), poly(organophosphazene), polylactides, polyglycolides, poly(dioxanones), polyhydroxybutyrate, polyhydroxyvalyrate, polyhydroxybutyrate/valerate copolymers, poly(vinyl pyrrolidone), polycyanoacrylates, polyurethanes, polysaccharides, and combinations thereof. 
     
     
       12. The composite of  claim 1 , wherein the second polyol comprises poly(caprolactone), poly(lactide), poly(glycolide), and/or combinations thereof. 
     
     
       13. The composite of  claim 1 , further comprising a porogen. 
     
     
       14. The composite of  claim 1 , further comprising a bioactive agent. 
     
     
       15. The composite of  claim 14 , wherein the bioactive agent is selected from the group consisting of antiviral agent, antimicrobial agent, antibiotic agent, amino acid, peptide, protein, glycoprotein, lipoprotein, antibody, steroidal compound, antibiotic, antimycotic, cytokine, vitamin, carbohydrate, lipid, extracellular matrix, extracellular matrix component, chemotherapeutic agent, cytotoxic agent, growth factor, anti-rejection agent, analgesic, anti-inflammatory agent, viral vector, protein synthesis co-factor, hormone, endocrine tissue, synthesizer, enzyme, polymer-cell scaffolding agent with parenchymal cells, angiogenic drug, collagen lattice, antigenic agent, cytoskeletal agent, mesenchymal stem cells, bone digester, antitumor agent, cellular attractant, fibronectin, growth hormone cellular attachment agent, immunosuppressant, nucleic acid, surface active agent, and penetraction enhancer. 
     
     
       16. The composite of  claim 1 , wherein the porosity is at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90%. 
     
     
       17. The composite of  claim 1 , wherein the porosity is in a range of 30% to 45%. 
     
     
       18. The composite of  claim 1 , wherein the composite comprises pores or channels that can support the in-growth of cells after implantation. 
     
     
       19. The composite of  claim 1 , wherein the second polyol is a polyester polyol. 
     
     
       20. The composite of  claim 1 , being configured for the repair of a simple fracture, compound fracture or non-union; as an external fixation device or internal fixation device; for joint reconstruction, arthrodesis, arthroplasty or cup arthroplasty of the hip; for femoral or humeral head replacement; for femoral head surface replacement or total joint replacement; for repair of the vertebral column, spinal fusion or internal vertebral fixation; for tumor surgery; for deficit filling; for discectomy; for laminectomy; for excision of spinal tumors; for an anterior cervical or thoracic operation; for the repairs of a spinal injury; for scoliosis, for lordosis or kyphosis treatment; for intermaxillary fixation of a fracture; for mentoplasty; for temporomandibular joint replacement; for alveolar ridge augmentation and reconstruction; as an inlay osteoimplant; for implant placement and revision; for sinus lift; for a cosmetic procedure; for revision surgery; for revision surgery of a total joint arthroplasty; and for the repair or replacement of the ethmoid, frontal, nasal, occipital, parietal, temporal, mandible, maxilla, zygomatic, cervical vertebra, thoracic vertebra, lumbar vertebra, sacrum, rib, sternum, clavicle, scapula, humerus, radius, ulna, carpal bones, metacarpal bones, phalanges, ilium, ischium, pubis, femur, tibia, fibula, patella, calcaneus, tarsal bones or metatarsal bones. 
     
     
       21. The composite of  claim 1 , wherein the polyisocyanate comprises lysine triisocyanate (LTI). 
     
     
       22. The composite of  claim 21 , wherein the first polyol comprises PEG. 
     
     
       23. The composite of  claim 1 , wherein the NCO-terminated prepolymer comprises about 14 wt % to about 26 wt % NCO. 
     
     
       24. The composite of  claim 1 , wherein the NCO-terminated prepolymer comprises about 23 wt % NCO. 
     
     
       25. The composite of  claim 1 , wherein the NCO-terminated prepolymer comprises a viscosity of about 21,000 cP. 
     
     
       26. The composite of  claim 1 , further comprising a polysaccharide filler. 
     
     
       27. The composite of  claim 26 , wherein the polysaccharide filler comprises hyaluronic acid (HA), carboxymethylcellulose (CMC), or combinations thereof. 
     
     
       28. The composite of  claim 26 , comprising about 10 wt % to about 35 wt % of the polysaccharide filler. 
     
     
       29. The composite of  claim 1 , wherein the first polyol is the same as the second polyol. 
     
     
       30. The composite of  claim 1 , further comprising a catalyst. 
     
     
       31. The composite of  claim 1 , wherein the first polyol is a polyether polyol. 
     
     
       32. A biodegradable composite, comprising:
 a plurality of bone particles; 
 a biodegradable polymer that includes a NCO-terminated prepolymer, the NCO-terminated prepolymer including a polyisocyanate and a first polyol, and a second polyol; and 
 wherein the composite in a hardened state is biodegradable and has a porosity of at least 3%.